Project Background. Posttraumatic stress disorder (PTSD) is a common mental health condition, with over 500,000 Veteran Affairs (VA) patients diagnosed with PTSD in 2010. The significant mortality and morbidity associated with PTSD underscore the importance of safe and effective treatments for this population. Substantial numbers of Veterans with PTSD present with multiple and complex symptomatology such as co- occurring pain, anxiety and insomnia, and are commonly prescribed opioid and benzodiazepine medications to treat these symptoms. Yet, potential interactions between opioids and benzodiazepines pose serious risks to patients who take them, with the most serious risks including fall-related injuries caused by over-sedation and death due to respiratory depression. Despite these known risks, limited information exists on the national prevalence of opioids and benzodiazepines prescribed concurrently, their use among patients at elevated risk of severe adverse events, such as those with problematic alcohol use, suicide risk and advanced age, or the comparative safety of these medications among those diagnosed with PTSD. Project Objectives. The specific aims of this project include to 1a) estimate the annual prevalence of any (>30-days) and long-term (>90-days) concurrent opioid and benzodiazepine use among patients with documented PTSD, 1b) estimate the annual prevalence of alcohol misuse, suicide risk and the elderly among patients with PTSD who are prescribed benzodiazepines and opioids concurrently, 2) assess whether VA patients with PTSD receiving opioids and benzodiazepines concurrently are at increased risk of all cause mortality and fractures, as compared to those receiving opioids only, benzodiazepines only and nonusers of these medications, and 3) test if alcohol misuse and advanced age are associated with increased risks of all cause mortality and fractures among VA patients with PTSD who are prescribed opioids and benzodiazepines concurrently, as compared to those who screen negative for alcohol misuse or who are <65 years old. Project Methods. This proposed retrospective cohort study will use data from the VA's Corporate Data Warehouse (CDW) and VA-CMS (Medicare and Medicaid) datasets to assess adverse events and VHA Vital Status Files to assess mortality. Eligible participants received care at a VA facility and were diagnosed with a PTSD diagnosis during fiscal years (FY) 2010-2011. Aim 1a will use gender-specific logistic regressions to estimate the annual prevalence of any (>30-days) and long-term (>90-days) concurrent use of opioids and benzodiazepines among patients receiving VA care and diagnosed with PTSD. Aim 1b will use gender-specific logistic regressions to estimate the prevalence of comorbid alcohol misuse, suicide risk and advance age (> 65 years old) among concurrent opioid and benzodiazepine users. Aim 2 will estimate the relative risk of mortality and fractures in FY 2011-2012 among new concurrent opioid and benzodiazepine users, as compared to propensity score matched users of benzodiazepines only, opioids only and nonusers of these medications, using hazard ratios from Cox proportional regression models. Aim 3 will test if the risks of all cause mortality and fractures among patients who are newly prescribed opioids and benzodiazepines concurrently are increased due to comorbid alcohol misuse and advanced age using Cox proportional regression models. Impacts. Knowledge gained from this proposal will support VA efforts to develop a national provider-level opioid surveillance system to reduce non-recommended prescribing practices, including concurrent prescribing of opioids and benzodiazepines, by identifying subsets of the population at greater risk of adverse events. Results will educate patients and providers with respect to two of the most important adverse events, death and fractures, associated with these medications, thereby informing clinical care decisions. Further, findings will provide critical information needed for development of computerized clinical decision support interventions designed to educate patients and providers about risks associated with these medications.